Intermittent dosing of daily antiretroviral therapy (ART) showed no difference in efficacy as continuous regular daily dosing in maintaining viral suppression when ART supplies are limited, according to a systematic review and meta-analysis.
On an intermittent dosing ART schedule, 3.1% of people experienced virologic failure, compared to 3.3% on a continuous ART schedule, for a risk difference of 0 (95% CI -0.01 to 0.02, P=0.54), reported Cassandra Fairhead, MBBS, of the University of Liverpool in England, at the International AIDS Society Conference on HIV Science in Kigali, Rwanda.
“It is essential that people living with HIV have access to uninterrupted person-centered care, including ART,” Fairhead said. “However, in the evolving funding crisis, this access is at risk. There are widespread reports of individuals already interrupting art due to clinics closing overnight.”
UNAIDS has found that 46% of surveyed countries are experiencing supply chain disruption of ART, and an additional 1-3 million HIV-related deaths and 4-11 million new infections are predicted in the next 5 years as a result of the shortages, she said.
“For countries with urgent drug shortages, extending ART supplies could have clinical benefits for people with HIV and population benefits of minimizing HIV transmission,” Fairhead said.
The researchers combed PubMed, MEDLINE, and ClinicalTrials.gov for randomized controlled trials of triple ART taken three to six times a week versus daily, defining efficacy of ART as maintaining a viral load at or below 50 copies/mL.
They identified eight trials with 1,346 people, including 22% females. The studies included people who had been virally suppressed for at least 3 months on daily ART, excluding pregnant people and, in most studies, those with hepatitis B, low baseline CD4 counts, and genotypic resistance to study drugs. Two studies also excluded people with previous virologic failure.
Four of the studies assessed 5 days on, 2 days off; one study assessed 4 days on, 3 days off, two studies assessed 3 days on, 4 days off; and the last study used an alternating one day on/one day off schedule.
When analyzing the results with missing data considered treatment value, “results were very similar between intermittent and continuous ART,” Fairhead reported. In the four studies that assessed highly sensitive viral load, with HIV limits of detection of less than 2, 5, 10, and 20 copies/mL, the results were again similar between the arms.
“Because intermittent ART studies intentionally reduced dosing to almost the minimum safe schedule, suboptimal adherence could confer a high risk of treatment failure,” Fairhead said, but in the seven studies that measured adherence, all but one of the trials showed similar levels of adherence between both arms.
“Adherence was typically very high, above 90%,” Fairhead said. “The success of intermittent therapy in these trials may therefore have relied on excellent adherence.”
In the four studies that assessed quality of life (QoL) and treatment satisfaction, participants favored intermittent therapy in all four studies, with 59% of those on intermittent schedules reporting improved QoL versus 7% in the continuous groups. Further, 90% of participants reported that having weekends off ART made life easier.
In the four studies assessing treatment-emergent resistance, 69% of successful genotypes showed resistance with intermittent ART, compared to 67% with continuous ART, resulting in 1.9% in the intermittent groups and 2.1% in the continuous groups developing resistance. In the three trials that assessed d-dimers, highly-sensitive C-reactive protein, and IL-6, there were no differences between the groups except significantly lower d-dimers in one trial’s intermittent therapy group.
Eric Cioè-Peña, MD, MPH, MBA, of Hofstra/Northwell Health in Staten Island, N.Y., told MedPage Today that the “key takeaway is that intermittent ART dosing, particularly 4 to 5 days per week, can be a safe and effective stopgap measure for patients already virologically suppressed. It preserves efficacy and minimizes resistance when done carefully.”
However, it must be made clear that this approach is “rationing, not innovation,” added Cioè-Peña, who was not involved in the study.
“These patients are in this position because policymakers created an artificial scarcity by abruptly cutting lifesaving programs,” Cioè-Peña said. “Using clinical ingenuity to stretch existing resources is admirable, but we should not mistake it for a sustainable strategy. The U.S. must re-engage in global health in a meaningful and accountable way. Simultaneously, we need private-sector innovation to increase programmatic efficiency, and national governments must realign budgets toward keeping their people alive.”
Disclosures
The research was funded by International Treatment Preparedness Coalition.
Fairhead disclosed a relationship with Gilead Sciences.
Cioè-Peña disclosed no relationships with industry.
Primary Source
International AIDS Society Conference on HIV Science
Source Reference: Fairhead C, et al “Systematic review and meta-analysis of the efficacy of intermittent antiretroviral therapy dosing: a crisis response to the sudden cuts in USAID and PEPFAR funding” IAS 2025.
